Transmission of HIV-1 CTL escape variants provides HLA-mismatched recipients with a survival advantage

Chopera, Denis R; Woodman, Zenda; Mlisana, Koleka; Mlotshwa, Mandla; Martin, Darren P; Seoighe, Cathal; Treurnicht, Florette; Rosa, Debra Assis de; Hide, Winston; Karim, Salim Abdool

Transmission of HIV-1 CTL escape variants provides HLA-mismatched recipients with a survival advantage

Journal Article

2008

Journal Title

PLoS One

Link to Journal

http://journals.plos.org/plospathogens

Publisher

Public Library of Science

Publisher

University of Cape Town

Department

Institute of Infectious Disease and Molecular Medicine

Faculty

Faculty of Health Sciences

License

http://creativecommons.org/licenses/by/4.0

Abstract

Author Summary Following infection with HIV, it is well established that a person's genetic makeup is a major determinant of how quickly they will progress to AIDS. Particularly important is the class I Human leukocyte antigen (HLA) gene that is responsible for alerting the immune system to HIV's presence. One of the reasons our immune systems are unable to beat HIV is that the virus can mutate to forms that our HLA genes no longer recognise. However, some people have versions of the HLA gene (for example HLA-B*57 and HLA-B*5801) that are known to force HIV to tolerate mutations that damage its ability to reproduce. Slower HIV reproduction is thought to be one reason that HLA-B*57 and HLA-B*5801 positive people progress to AIDS more slowly than most other HIV infected persons. We report here on a study of HLA-B*57 and HLA-B*5801 negative women in which better control of disease tended to be associated with their being infected with viruses carrying mutations that have been previously shown to reduce replication. These mutations characterise viruses found infecting HLA-B*57 and HLA-B*5801 positive people. This indicates for the first time that HLA-B*57 or HLA-B*5801 negative people that are infected by such reproductively compromised viruses may also experience better survival prospects.